Method and means for gold-coating implantable intravascular devices

ABSTRACT

Implantable vascular prostheses, formed of synthetic, woven fibers are coated with a thin layer of metallic gold sufficient to create a continuous coating over the surfaces of the fibers that come into contact with blood. The coating is applied by vapor deposition or sputtering to coat the fibers without blocking or bridging the interstices formed by the intersection of the fibers.

This is a continuation-in-part of application Ser. No. 417,798, filedOct. 4, 1989, now abandoned, which is a continuation-in-part ofapplication Ser. No. 254,359, filed Oct. 5, 1988, now abandoned.

The present invention relates generally to implantable artificialgrafts, shunts, patches and valves and, more particularly, to methodsand means for limiting the formation of thromboses after such grafts,shunts, patches or valves have been surgically implanted into a livingrecipient.

BACKGROUND OF INVENTION

Surgical repair or replacement of major blood vessels or heart valvesdamaged by disease or injury is a difficult and delicate process. Wherethe blood vessel or valve involved has been damaged or has deterioratedto the point where it cannot be repaired, it must be replaced.

With respect to blood vessels, techniques have been developed to usearteries or veins from other parts of the patient's body, or from adonor, to substitute for the damaged or diseased body part. This resultsin a duality of required surgical procedures wherein a length of vesselsuitable for replacing the injured or diseased portion is removed fromone part of the body, or from the donor, and implanted at the site ofthe injury or disease.

The use of blood vessels from donors has been successfully carried out,but such procedures call for the suppression of the body's normal immunesystem antagonism toward the presence of foreign tissue. Although thisprocedure has become safer and more readily regulated, it requires drugswhich may have untoward side effects on the patient. Certainly, thesimpler and more straightforward a surgical procedure, the greater thelikelihood that the patient will tolerate it well and will make asatisfactory recovery.

More recently, artificial shunts, grafts, patches and heart valves havebeen developed to be surgically implanted to replace those found to bedamaged or defective. Such artificial expedients have been made frommaterials selected for their capacity to be tolerated well by the humanbody, to handle the requirements of fluid pressures demanded of theaffected blood vessel or valve, and to provide attachment sites for theanchoring of sutures and the formation of scar tissue. Among suchmaterials are tetrafluoroethylene (sold under the registered trademark"Teflon") and polyethylene glycol terephthalate (sold under theregistered trademark "Dacron"). Both are especially well-suited forproducing knitted, woven or braided implants grafts, or attachmentcuffs. Another material so used for shunts, grafts and patches is anexpanded microporous polytetrafluoroethylene sold under the registeredtrademark "Gore-Tex".

Examples of such an artificial heart valve are the valve manufactured bySt. Jude Medical and Edwards CVS Division of Baxter Healthcare, Inc. TheEdwards valve assembly consists generally of a rigid, rounded metallicvalve body or frame within which a metallic valve plate or leaflet isrotatably suspended. A cuff or attachment ring fashioned from one of thematerials described above surrounds the valve frame and provides anattachment site for fibrous tissue to infiltrate and anchor the valveassembly in place. The valve plate is shaped and pivoted to act as acheck valve against the backflow of blood, and is thus in intimatecontact with the stream of blood passing to or from the heart. A similarconstruction is utilized in the heart valve sold under the St. JudeMedical registered trademark. This valve utilizes a pair of leaflets asthe blood flows regulators.

Examples of vascular shunts are shown and described in U.S. Pat. Nos.4,167,045 (Sawyer) and 4,712,551 (Rayhanabad). Sawyer teaches a vascularshunt made from Dacron (Registered U.S. Trademark), coated withglutaraldehyde-polymerized proteins, aluminum or other substances.Sawyer also teaches that early attempts to use rigid, gold tubes asvascular shunts were unsuccessful.

Rayhanabad shows a multi-branched vascular shunt for temporary useduring surgery. The use of such a shunt enables blood flow to becontinued to vital organs even while a main blood vessel is beingtreated. For permanent implants, it is desirable to utilize a porousmaterial for the shunt or graft to allow for the infiltration of thePores by body tissue in order to firmly hold the shunt or graft inposition and to create a shunt "formed" from living tissue. This need isbalanced by the need to provide a liquid-tight conduit to operate as areplacement blood vessel. One approach to balancing these two needs isshown in U.S. Pat. No. 3,106,483 (Kline et al.), which acknowledges theprior use of artificial blood vessels formed by knitting, weaving orbraiding polymer synthetic filaments such as "Dacron" (Registered U.S.Trademark) or "Teflon" (Registered U.S. Trademark). Use of knitted,woven, or braided implants is said to offer advantages in providing aporous surface into which body tissue may grow after implantation; suchimplants also offer a secure underlay for suturing. Kline et al. teachthe use of an assimilatable coating within the graft which initiallycreates a liquid-tight conduit; the lining thereafter graduallydissolves into the blood stream leaving behind a porous network which bythis time has been infiltrated and filled by body tissue to fill thepores and provide a liquid-tight vessel.

U.S. Pat. No. 3,094,762 (Jeckel) teaches the use of Teflon (RegisteredU.S. Trademark) knitted or woven into a blood vessel graft. Dardik etal., in U.S. Pat. No. 3,974,526, teach the use of the human umbilicalcord as a vascular grafting material, including shaping and hardeningthe cord on a mandrel, chemically treating the umbilical cord to limitantigenicity, and using a reinforcing mesh to strengthen the resultingprosthesis.

The presence of thromboses or blood clots is of significant concern inany surgical procedure, and is also a most serious problem in usingarterial-venous shunts or artificial heart valves. Clotting frequentlyoccurs in dialysis shunts, requiring removal of the shunt, clearing andsurgical reimplantation. The formation and dislodging of a clot mayresult in the occlusion or blocking of a blood vessel, interrupting thelife-giving flow of blood to major organs of the body. Formation ofthromboses in surgically implanted arterial or venous grafts may resultbecause of such factors as the woven, porous nature of the graftmaterial a construction which may attract blood platelets or debris inthe blood stream. The graft's chemical composition, its compliance,and/or its electro-negativity, each of which may evoke a differenttissue reaction may also contribute to thrombosis. See, for example,Greisler, et al., "Plasma Polymerized Tetrafluoroethylene/PolyethyleneTerephthalate Vascular Prostheses", Arch. Surg., Vol. 124, pp. 967-972(August, 1989). This creates the attendant risk that once a mass ofdetritus reaches a significant weight and size, it may adhere to thewall of the blood vessel, progressively blocking the vessel, or it maybe dislodged by the flow of blood through the blood vessel and willtravel until it encounters a blood vessel having a diameter of less thanthat of the thrombus, causing a blockage.

Prevention of thromboses in implantable shunts has been addressed inU.S. Pat. No. 3,988,782 (Dardik et al.) wherein the use of "pre-clotted"or hardened lengths of human umbilical cord as homografts is taught. Theanti-thrombogenic properties of such homografts is, according to thepatent, a product of the hardening of the umbilical cord length used tomanufacture the homograft.

U S. Pat. No. 4,355,426 (McGregor) teaches the construction of ametallic porous vascular graft, which depends for its anti-thrombogenicproperties upon the formation of a smooth coating of tissue created bythe growth of nucleated cells from the blood stream over the poroussurface and sub-surface of the graft.

Ward et al. (U.S. Pat. No. 4,164,524) teach the technique of evacuatinggas nuclei trapped in the walls of blood-treatment devices to minimizethe presence of cavities within which blood platelets may collect tobegin the clotting process.

Other attempts at limiting the formation of thromboses have utilizedcoating materials applied to the grafts or shunts. U.S. Pat. No.4,718,907 (Karwoski et al.) teaches the use of a fluorinated coatingapplied electrically to the surfaces of an interwoven fabric tube. Braun(U.S. Pat. No. 4,265,928) teaches an anti-thrombogenic catheterdependent for its non-clotting properties upon the deposition of a thincoating of an ethylene-acrylic acid copolymer to the interior surface ofthe catheter.

Yet another approach to limiting the formation of thromboses is to usean anti-clotting agent, such as heparin, in the blood stream of thepatient. Use of heparin or any other anti-coagulant has the undesirableside effect of robbing the blood of its ability to clot in the event ofa traumatic injury. Attempts have been made to localize theanti-clotting effect of heparin as, for example, in U.S. Pat. No.4,704,131 (Noishiki et al.) who teach the formation of a heparinizedcollagen to be used as a material for constructing artificial grafts orshunts. Similarly, U.S. Pat. Nos. 4,676,975 and 4,678,660 (McGary etal.) teaches the manufacture of anti-thrombogenic thermoplasticincorporating an anti-thrombogenic agent such as heparin into a polymer.The anti-thrombogenic agent is thus dispersed throughout the materialused to construct the graft.

It has long been known that the use of gold in surgical procedures iswell-tolerated by the human body because gold is essentially chemicallyinert, meaning it does not react with such commonly available reagentsas sulfur, oxygen, water and the like. Gold is also electricallyconductive, a property which may aid in the dispersal of electricalcurrents that may promote thromboses.

Surgical uses of gold leaf are described in an article entitled "The Useof Charged Gold Leaf in Surgery" authored by Dr. John P. Gallagher andDr. Charles F. Geschickter, and Published in the Journal of the AmericanMedical Association on Sep. 21, 1964. Drs. Gallagher and Geschickterdescribe a process well known to all those who have used gold leaf inthe painting of signs, namely, the use of a camel's hair brush to impartan electrical charge to the gold leaf and the subsequent application ofthe gold leaf to a desired surface. It was found that gold wasassimilated by the body without adverse reactions and without apparentlyrequiring the use of drugs to control reactions of the body's immunesystem.

The therapeutic properties of gold, together with the body's long-termtolerance to the presence of gold have been recognized by the medicalprofession.

For example, the use of gold in the treatment of rheumatoid arthritis isdescribed by D. L. Scott et al. in an article entitled "CombinationTherapy With Gold and Hydroxychloroquinine in Rheumatoid Arthritis: aProspective, Randomized, Placebo-Controlled Study" (Br. J. Rheumatology1989 Apr: 28(2); 128-33).

Gold has also been used in plastic surgery, demonstrating the long termtolerance of tissue for this metal. See, for example, P. Chapman, etal., "Results of Upper Lip Loading in the Treatment of LagophthalmosCaused by Facial Palsy" (Br J. Plastic Surgery 1988 Jul; 31(4): 369-72);and A. R. Newman, et al., "The Correction of Seventh Nerve PalsyLagophthalmos with Gold Lid Load" (Ann Plastic Surgery 1988 Feb; 22(2):142-5.

U.S. Pat. No. 4,054,139 (Crossley) teaches the use of metals such assilver and gold used in catheters to prevent bacterial infection. Suchmetals are applied in small amounts throughout the material used to formthe catheter but Crossley does not suggest the use of a continuous metalcoating to present an anti-thrombotic surface for permanentimplantation.

U.S. Pat. No. 4,743,253 (Magladry) teaches the application of gold to ametallic compression ring used in a suture ring assembly for heartvalves. This is an application which does not address the particularproblems of preventing the formation of thromboses on the metallic orrigid portions of the heart valve itself nor on the suture ring and thefabric used to form an anchoring site for the ring. The suture ring ofMagladry is ductile and electrically conductive but must be covered by afabric to form an anchoring site for suturing to the heart.

It may thus be seen that the characteristics required for theconstruction of a successfully implantable graft, shunt, patch or valveare the ability of the human body to tolerate the presence of thematerial from which the implant is formed, the provision of a somewhatporous construction to enable body tissue to infiltrate the implant,thus holding it firmly in place, the resistance of the implant to leaks,particularly where used in a blood vessel subjected to the pressurepulses created by the pumping of blood by the heart and the provision ofa mechanism whereby the formation of thromboses within or upon theimplant is limited. Such implant should, ideally, be capable of usewithout requiring anti-coagulant drugs or compounds and should utilizematerials which are uniformly non-reactive with body fluid constituentsor tissues.

In my experience, many replacement heart valves are manufactured frompyrolitic carbon, and use fabric cuffs (typically Dacron® or Teflon®) tosurround the suturing ring for use as an attachment site for suturesand, eventually, for infiltration by fibrous tissue. To my knowledge, novalves are presently available which provide gold as a protectivecoating for the hard surfaces as well as the individual fabric fibers.Such a coating should also ideally be highly electrically conductive todecrease the preserve of electrical currents with a concomitant decreasein the tendency for unwanted cell deposition to occur.

Meeting these criteria is of paramount importance given the rapiddevelopment of artificial implantable organs and replacement devicessuch as heart valves and the like which come into intimate contact witha patient's blood stream. Implants which otherwise function perfectly asreplacements for body parts will continue to be unsuitable if suchreplacements, by their construction, provide sites at which thrombosescan form. As discussed above, it has also been learned that the presenceof electrical charges and the like provide a breeding ground for theformation of thromboses, and the presence or strength of these currentsshould be limited or dissipated.

Heretofore, attempted solutions to these problems have focused upon theinterreaction of blood constituents with the material from which theimplants are formed.

BRIEF SUMMARY OF THE INVENTION

Vascular grafts, shunts, patches and heart valves are provided with ametallic coating which is chemically inert, readily deformable,hydrophobic, electrically conductive and non-reactive with body tissueor fluids.

In a first, preferred embodiment of the present invention, syntheticvascular shunts and patches are provided with gold coatings applied byvapor-deposition or by sputtering. The use of the vapor-depositiontechnique is described in U.S. Pat. No. 4,167,045 (Sawyer) and inarticles entitled "Vacuum Metallized Shielding" (distributed byDeep-Coat Metallizing, Inc. of Lemont, Illinois), and R. Allen Myers."An Introduction to Functional Thin Films" presented at the June, 1987EMI/RFI Symposium of Plastics Engineers. Sputtering is described in "TheHandbook of Thin Film Technology" edited by Leon Maissel and RheinhardtGlang (McGraw-Hill Publishing Co., 1970) at pages 3-30 through 3-37.

Such a coating should be capable of flexing with the implant as theimplant is twisted into position for permanent attachment, as theimplant may flex during pulsative transmission of blood therethrough.Such coating should also preserve the porous construction of the graftto allow for the infiltration of fibrous tissue.

In yet another preferred embodiment of the invention, artificial heartvalves and the suturing cuffs used to anchor such valves are similarlycoated with gold prior to implantation.

These and further aspects of the present invention will be more apparentupon a consideration of the accompanying drawings wherein:

FIG. 1 is a sectional view of a portion of an implant in the form of avascular shunt or graft embodying the present invention;

FIG. 2 is an implantable patch embodying the present invention;

FIG. 3 is a scanning electron microscope photograph taken at 15 KU #20×magnification showing vapor-deposition coating of a Dacron (RegisteredU.S. Trademark) implant;

FIG. 4 shows the shunt of FIG. 3 at 15 KU 86× magnification; and

FIG. 5 shows a heart valve and suture cuff generally of the typediscussed herein.

DETAILED DESCRIPTION OF THE INVENTION

It is well-known that gold may be applied to a substrate or an articleby the techniques of vapor-deposition or sputtering.

The present invention involves the construction of implantable, grafts,shunts, patches, heart valves or other devices to be incorporated aspart of the vascular system of a living body consistent with theforegoing teachings of the prior art and providing the finished implantswith a coating of gold. The coating is applied to the surfaces of theimplant intended to come into contact with the patient's blood streamthereby providing a lining or coating which is chemically inert andwhich has been observed and predicted to inhibit the formation ofthromboses and possibly infection.

A preferred embodiment of the present invention involves the manufactureof synthetic vascular grafts, shunts and cuffs from products such asDacron (Registered U.S. Trademark), Teflon (Registered U.S. Trademark)or Gore-Tex (Registered U.S. Trademark) materials, and the subsequentapplication of a layer of gold thereto. It is expected that the layer ofgold may be applied either during or after the manufacturing process,depending upon the specific manufacturing steps undertaken by theproducer of such implants. For example, for implants formed by "rolling"a cylinder from a flat piece of synthetic material, it is expected thatgold may be applied to the material before or after such rolling occurs.Where material is drawn, as over a mandrel, to form a seamless tube, itis expected that the vapor deposition or sputtering techniques willinduce the gold to adhere tightly to the inner and outer walls of theimplant.

In a first, preferred embodiment, a vascular shunt manufactured byMeadox Medicals, Inc. of Oakland, N.J. 07436 from Dacron (RegisteredU.S. Trademark) and sold under the trademark "Cooley 2" is coated withgold by the vapor-deposition process. As seen in FIG. 1, graftconstruction 10 includes a length of cylindrical shunt or graft 11 towhich gold has been applied to outer wall 12 and inner wall 13 and theDacron (Registered U.S. Trademark) construction is characterized bynumerous interstices created by the woven nature of the fabric, as seenin FIGS. 3 and 4. It has been found desirable to maintain the opennessof these interstices to provide sites for infiltration by fibrous bodytissue. Such infiltration stabilizes and firmly holds the graft 11 afterimplantation. As shown in FIGS. 3 and 4, photomicrographic examinationestablishes that the individual fibers making up shunt 11 are coatedevenly with gold without bridging or otherwise blocking the intersticesformed by the weave pattern. It is expected that the gold so appliedwill penetrate within the intersticial fiber bundles so that the coatingwill extend inward from both the inner and outer surfaces.

The variety of vascular grafts manufactured by W. L. Gore and Associatesuse a fabric identified by the registered trademark Gore-Tex. Theessential characteristic of Gore-Tex (Registered U.S. Trademark) fabricis a controllable and selectable distribution of pore sizes, making thematerial readily adaptable to create the type of pore distribution whichwill allow the implant to attract and support the growth of body tissueto hold the implant in place.

Another method of manufacture for graft 10 may be to vapor-deposit goldon an outer surface 14 of graft 11, then to turn graft 11 inside out toposition gold layer 12 within shunt 11 along the path of blood flow.

Referring now to FIG. 2, the numeral 20 indicates generally a patch 21prepared in accordance with the teachings of the present invention. Alayer 22 of gold is applied to be coextensive with patch 21, and thepatch may be trimmed to meet selected surgical requirements.

In the practice of a first, preferred embodiment of the invention, patch20 has a coating 22 applied by vapor-deposition of metallic gold asdescribed hereinabove.

Preferably, the use of gold with synthetic implants is contemplated.However, it is also expected that the techniques described herein areapplicable to shunts such as those described in Dardik, et al. (U.S.Pat. Nos. 3,974,526 and 3,988,782).

Referring now to FIG. 5, the numeral 30 indicates generally anartificial implantable heart valve. The particular valve herein depictedis one manufactured and sold under the registered trademark "St. JudeMedical", and consists of a generally circular valve housing 31 withinwhich valve leaflets 32 and 33 are pivotally mounted. Leaflet 32 issupported at pivot points 34 and 35, while leaflet 33 is supported atpivot points 36 and 37. Leaflets 32 and 33 are shaped and suspended insuch fashion as to pivot open when blood is pumped or drawn therethrough, and to pivot shut, preventing backflow, between heart beats.

When implanted, valve housing 31 is surrounded by suture cuff 38 formed,in one embodiment, from bio-compatible Dacron® double velour vasculargraft material. Cuff 38 is fashioned to eliminate seams along its outersurface to reduce the availability of sites for the generation ofthromboses.

In the preferred practice of the present invention, valve 30 and cuff 38are coated with gold by vacuum-deposition. Coating valve 30 provides thebenefits described above with respect to prevention of thromboses,limiting of electrical currents, inertness and bio-compatibility. Goldcoatings also help keep leaflets 32 and 33, and pivot points 34, 35, 36and 37 clear of tissue and detritus to assure the reliable operation ofthe valve. It is also expected that the bacteriacidal properties of goldwill aid in preventing or alleviating bacterial infections at theimplant site.

Coating suture cuff 38 with gold provides these same benefits andpreserves the presence of open interstices for the infiltration offibrous tissue that will eventually anchor the cuff 30 and valve housing31 into permanent contact with the heart tissue.

The use of the terms "vacuum deposition" or "sputtering" are notintended to be limiting, but to include other application techniqueswhich allow devices such as those described herein to be protected by acoating of metallic gold while meeting the requirements of the presentinvention.

The present invention has been described in terms consistent with theimplantation of artificial grafts, shunts, patches and valves in humanbeings, but it should be understood that the present invention may alsobe used in other animals as well.

While the foregoing has presented certain specific embodiments of thepresent invention, it is to be understood that these embodiments havebeen presented by way of example only. It is expected that othersskilled in the art will perceive variations which, while differing fromthe foregoing, do not depart from the spirit and scope of the inventionas herein described and claimed and no limitation as to the descriptionof the present invention is hereby made or intended.

What is claimed is:
 1. In a vascular graft for implanting into the bloodcirculatory system of a living recipient, said graft formed from a wovenfabric of `synthetic` material polymeric substrate, said fabriccharacterized by interstices created by the woven nature of the fabricanother, said graft having a surface formed by said fabric, said surfacefor exposure to the blood of said recipient, the improvementcomprising:a thin layer of metallic gold applied to coat said fabricforming said surface, said layer applied to leave said interstices openand unblocked.
 2. The construction of claim 1 wherein said vasculargraft further comprisesa tubular body formed from said fabric, saidtubular body having an inner wall, said inner wall coated with gold. 3.The construction of claim 1 wherein said layer of metallic gold isvapor-deposited onto said vascular graft.
 4. The construction of claim 1wherein said layer of metallic gold i sputtered onto said vasculargraft.
 5. The construction of claim 1 wherein said synthetic material istetrafluoroethylene polymer.
 6. The construction of claim 1 wherein saidsynthetic material is polyethylene glycol terephthalate.
 7. Theconstruction of claim 1 wherein said synthetic material is expandedmicroporous polytetrafluoroethylene.